Letter abstract
Nature Genetics 39, 251 - 258 (2007)
Published online: 21 January 2007 | doi:10.1038/ng1949
Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation
Godfried W van der Heijden1,6, Alwin A H A Derijck1,6, Eszter Pósfai2, Maud Giele1,5, Pawel Pelczar2,5, Liliana Ramos1, Derick G Wansink3, Johan van der Vlag4, Antoine H F M Peters2 & Peter de Boer1
In mammalian males, the first meiotic prophase is characterized by formation of a separate chromatin domain called the sex body1. In this domain, the X and Y chromosomes are partially synapsed and transcriptionally silenced, a process termed meiotic sex-chromosome inactivation (MSCI)2, 3. Likewise, unsynapsed autosomal chromatin present during pachytene is also silenced (meiotic silencing of unsynapsed chromatin, MSUC)2, 4, 5. Although it is known that MSCI and MSUC are both dependent on histone H2A.X phosphorylation mediated by the kinase ATR, and cause repressive H3 Lys9 dimethylation4, the mechanisms underlying silencing are largely unidentified. Here, we demonstrate an extensive replacement of nucleosomes within unsynapsed chromatin, depending on and initiated shortly after induction of MSCI and MSUC. Nucleosomal eviction results in the exclusive incorporation of the H3.3 variant, which to date has primarily been associated with transcriptional activity. Nucleosomal exchange causes loss and subsequent selective reacquisition of specific histone modifications. This process therefore provides a means for epigenetic reprogramming of sex chromatin presumably required for gene silencing in the male mammalian germ line.
- Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
- Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland.
- Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
- Nephrology Research Laboratory, Division of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
- Current addresses: Orthopedic Research Laboratory, Department of Orthopedics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands (M.G.) and Institute of Laboratory Animal Science, University of Zürich, Sternwartstrasse 6, CH 8091 Zürich, Switzerland (P.P.).
- These authors contributed equally to this work.
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